Linking sugars

08 January 2007

Researchers in Canada have found a cheaper way of making glycans, complex carbohydrate structures found in biological systems.

Glycans are found in cells, often bonded to proteins as structures called glycoproteins, where they have various functions. But, said Stephen Withers, an enzymologist, from the University of British Columbia, Vancouver, problems with making glycans could explain why their role in normal and pathological biology remains poorly understood.

"It removes the need to access sugar nucleotides, which are often synthetically challenging targets, by forming them in situ from synthetically accessible glycosides" - David Jakeman

The individual carbohydrate building blocks in glycans are linked in a variety of stereochemical orientations so it can be difficult to make glycans using traditional synthetic chemistry, said Withers. In nature, the linking process is catalysed by glycosyltransferase enzymes, and using these enzymes is a good alternative method to make glycans, he added. However, glycosyltransferases use nucleotide-bound sugars as their sugar source and these are expensive.

Withers and co-workers have found that nitrophenyl glycosides can be used as alternative, cheaper substrates for glycosyltransferases, as long as a catalytic amount of nucleotide phosphate is present. The enzyme transfers the sugar from the nitrophenyl glycoside onto the nucleotide phosphate and uses the resulting sugar compound to make the glycan by its normal mechanism. This releases the nucleotide phosphate for further cycles.

David Jakeman, an expert in carbohydrate enzymology from Dalhousie University, in Halifax, Canada, explained that glycosyltransferases are involved in a myriad of important biochemical and cellular functions. This work provides a new way to make their substrates, he said. 'It removes the need to access sugar nucleotides, which are often synthetically challenging targets, by forming them in situ from synthetically accessible glycosides.'

According to Withers, the next step will be to explore the generality of this approach using a range of glycosyltransferases. He suggests that modifying the enzymes could give faster reaction rates using the artificial substrates.